The field of the invention is antibiotic compositions, kits, and methods of use thereof.
Numerous antibiotic compositions are known, some exhibiting antibiotic activity against a broad spectrum of microorganisms, and others exhibiting antibiotic activity only against one or a few narrow classes of organisms, such as gram-positive bacteria. One shortcoming associated with all known antibiotics is that microorganisms, especially bacteria, can become resistant to an antibiotic to which they were previously susceptible under certain conditions. Human pathogens are among the microorganisms which are capable of developing antibiotic resistance. Thus, even though certain antibiotics are highly efficacious against a broad range of microorganisms, it is necessary to continually develop new antibiotic compositions in order to remain ahead of the development of antibiotic-resistant microorganisms or to develop antibiotics that are, due to their intrinsic characteristics of antimicrobial action, less likely to generate resistant strains. Further, the continuing identification of new antibiotics will reduce the likelihood that a strain of microorganism will arise which is resistant to most or all known antibiotics.
Bacterial resistance to antibiotics is an increasing problem of potentially pandemic proportions, both in the United States and abroad. In one review, more than 31% of 17,000 bacterial isolates of Streptococcus pneumoniae obtained from patients were identified as being resistant to penicillin. Furthermore, in 1997, three untreatable vancomycin-resistant cases were reported in Camden, N.J. (Murray, 1977, Am. J. Med. 102:284-293).
The need for anti-microbial products has increased in the past few years, due to the emergence of multi-drug resistant bacterial infections. The U.S. Centers for Disease Control and Prevention estimate that antibiotics are one of the most widely used classes of drugs, both in the United States and worldwide. Extensive research efforts are underway to identify potential antibiotic candidate compounds. The present invention satisfies the continuing need for new antibiotic compositions.
The invention relates to a method of inducing death of a microorganism. The method comprises contacting the microorganism with a composition comprising a substantially purified eukaryotic histone H1 protein. Death of the microorganism is thereby induced. In one embodiment the microorganism is a human pathogen such as a bacterium selected from the group consisting of Escherichia coli, Klebsiella pneumoniae, a Shigella species, Serratia marcesceans, Bacillus cereus, Bacillus subtilis, Pseudomonas aeruginosa, Proteus morgani, Staphylococcus albus, Salmonella typhimurium, Salmonella enteritidis, and Bacillus megaterium. In another embodiment, the eukaryotic histone H1 protein is chemically modified, such as a polyethylene glycol-derivated eukaryotic histone H1 protein.
The invention also relates to a method of inhibiting growth of a microorganism. This method comprises contacting the microorganism with a composition comprising a substantially purified eukaryotic histone H1 protein.
The invention further relates to an antimicrobial pharmaceutical composition comprising a substantially purified eukaryotic histone H1 protein and a pharmaceutically acceptable carrier. The composition may, for example, be in the form of a suspension suitable for injection or infusion into an animal tissue, such as blood. The composition may also be, for example, in the form of a wound dressing. The wound dressing may be selected from the group consisting of a creme, a gel, an absorbent material, and a physiologically degradable material. In one embodiment, the composition further comprises a supplemental antibiotic, such as one selected from the group consisting of histones H2A, H2B, H3, H4, and H5, penicillin, streptomycin, vancomycin, bacitracin, polymyxin, neomycin, chloramphenicol, chlortetracycline, ciprofloxacin, tobramiycin, erythromycin, gentamicin, gramicidin, oxytetracycline, norfloxacin, a salt of an antibiotic, and an ester of an antibiotic.
The invention still further relates to a kit comprising the composition of the invention and an instructional material selected from the group consisting of an instructional material which describes use of the antimicrobial composition to kill a microorganism and an instructional material which describes use of the antimicrobial composition to arrest the growth of a microorganism. The composition may, for example, be in a unit dosage form. In one embodiment, the kit further comprises a histone H1 antidote such as heparin.
The invention also relates to a method of treating a microbial infection in an animal. This method comprises administering an antimicrobial composition comprising a substantially purified eukaryotic histone H1 protein to the animal. The animal may be a mammal such as a human. Furthermore, the composition may, for example, be administered to the animal by a route selected from the group consisting of an oral route, an intraperitoneal route, an intravenous route, and a topical route.
The invention further relates to a method of inhibiting microbial growth at a site. This method comprises providing an antimicrobial composition comprising a eukaryotic histone H1 protein to the site. The composition may be provided at the site by incorporating the composition into the site, for example. In various embodiments, the site is located on or within a foodstuff or on or within an animal tissue. In other embodiments, the composition is provided to an animal tissue during a surgical procedure or to a site by providing the composition to a surface which contacts the site. The surface may, for example, be selected from the group consisting of a surface of a wound of an animal and a surface of a surgical implement. In another embodiment, the site is an internal portion of an animal and wherein the composition is provided to the site by providing a biodegradable implant comprising the composition to the site.
The invention still further relates to a supplemented animal feed comprising an animal feed supplemented with an antimicrobial composition comprising a substantially purified eukaryotic histone H1 protein.
In addition, the invention relates to a method of improving growth of a non-human animal. This method comprising feeding the animal the supplemented animal feed of the invention. The non-human animal may, for example, be a farm animal.
The invention also relates to a method of preparing an animal vaccine. This method comprises adding a eukaryotic histone H1 protein to a preparation of a microorganism. The microorganism is thereby killed, and the preparation of the killed microorganism comprises the vaccine.
The invention further relates to a method of vaccinating an animal, the method comprising administering to the animal the vaccine of the invention.
The invention still further relates to another method of vaccinating an animal. This method comprising administering to the animal a composition comprising an attenuated or killed form of a microorganism and a substantially purified eukaryotic histone H1 protein.